LOW-MOLECULAR-WEIGHT NEUROKININ-NK(2) ANTAGONISTS

被引：14
|
作者：
SMITH, PW
MCELROY, AB
PRITCHARD, JM
DEAL, MJ
EWAN, GB
HAGAN, RM
IRELAND, SJ
BALL, D
BERESFORD, I
SHELDRICK, R
JORDAN, CC
WARD, P
机构：
[1] GLAXO GRP RES LTD, DEPT MED CHEM, GREENFORD UB6 0HE, MIDDX, ENGLAND
[2] GLAXO GRP RES LTD, DIV PHARMACOL, WARE SG12 0DP, HERTS, ENGLAND
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1993年 / 3卷 / 05期
关键词：
D O I：
10.1016/S0960-894X(00)80695-2
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A deletion - optimization strategy based on an initial heptapeptide lead structure 1 led to potent and selective neurokinin NK2 antagonists 5 (pK(B)=9.3) and 9 (pK(B)=7.9) of substantially reduced molecular size. Tetrapeptide 5 (0.1 mumol/Kg i.v.) potently inhibits NK2 agonist-induced bronchoconstriction in guinea-pigs. Whilst less potent than 5 in vivo, the dipeptoid 9 (5 mumol/Kg i.v.) had a significantly longer biological half-life (> 2 h), and provides a potential lead towards non-peptide analogues.
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页码：931 / 936
页数：6
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